Gut Microbiota as a Target for Preventive and Therapeutic Intervention against Food Allergy.

The gut microbiota plays a pivotal role in immune system development and function. Modification in the gut microbiota composition (dysbiosis) early in life is a critical factor affecting the development of food allergy. Many environmental factors including caesarean delivery, lack of breast milk, drugs, antiseptic agents, and a low-fiber/high-fat diet can induce gut microbiota dysbiosis, and have been associated with the occurrence of food allergy. New technologies and experimental tools have provided information regarding the importance of select bacteria on immune tolerance mechanisms. Short-chain fatty acids are crucial metabolic products of gut microbiota responsible for many protective effects against food allergy. These compounds are involved in epigenetic regulation of the immune system. These evidences provide a foundation for developing innovative strategies to prevent and treat food allergy. Here, we present an overview on the potential role of gut microbiota as the target of intervention against food allergy.

Extensively hydrolyzed casein formula containing Lactobacillus rhamnosus GG reduces the occurrence of other allergic manifestations in children with cow's milk allergy: 3-year randomized controlled trial.

BACKGROUND: Children with cow's milk allergy (CMA) have an increased risk of other allergic manifestations (AMs). OBJECTIVE: We performed a parallel-arm randomized controlled trial to test whether administration of an extensively hydrolyzed casein formula (EHCF) containing the probiotic Lactobacillus rhamnosus GG (LGG) can reduce the occurrence of other AMs in children with CMA. METHODS: Children with IgE-mediated CMA were randomly allocated to the EHCF or EHCF+LGG groups and followed for 36 months. The main outcome was occurrence of at least 1 AM (eczema, urticaria, asthma, and rhinoconjunctivitis). The secondary outcome was tolerance acquisition, which was defined as the negativization of a double-blind food challenge results at 12, 24, and 36 months. AMs were diagnosed according to standardized criteria. Tolerance acquisition was evaluated every 12 months. RESULTS: A total of 220 children (147 boys [67%]) with a median age of 5.0 months (interquartile range, 3.0-8.0 months) were randomized; 110 children were placed in the EHCF group, and 110 children were placed in the EHCF+LGG group. In the complete case analysis the absolute risk difference for the occurrence of at least 1 AM over 36 months was -0.23 (95% CI, -0.36 to -0.10; P < .001), and the absolute risk difference for the acquisition of cow's milk tolerance was 0.20 (95% CI, 0.05-0.35; P < .01) at 12 months, 0.24 (95% CI, 0.08-0.41; P < .01) at 24 months, and 0.27 (95% CI, 0.11-0.43; P < .001) at 36 months. In the sensitivity analysis the effect size of the main outcome was virtually unchanged when the occurrence of AMs was assigned to all 27 missing children. CONCLUSIONS: EHCF+LGG reduces the incidence of other AMs and hastens the development of oral tolerance in children with IgE-mediated CMA.

Formula selection for management of children with cow's milk allergy influences the rate of acquisition of tolerance: a prospective multicenter study.

OBJECTIVES: To prospectively evaluate the effect of different dietary management strategies on the rate of acquisition of tolerance in children with cow's milk allergy (CMA). STUDY DESIGN: Otherwise healthy children (aged 1-12 months) diagnosed with CMA were prospectively evaluated. The study population was divided into 5 groups based upon the formula used for management: (1) extensively hydrolyzed casein formula ([EHCF], n = 55); (2) EHCF + Lactobacillus rhamnosus GG [LGG], n = 71); (3) hydrolyzed rice formula (RHF, n = 46); (4) soy formula (n = 55); and (5) amino acid based formula (n = 33). A food challenge was performed after 12 months to assess acquisition of tolerance. RESULTS: Two hundred sixty children were evaluated (167 male, 64.2%; age 5.92 months, 95% CI 5.48-6.37; body weight 6.66 kg, 95% CI 6.41-6.91; IgE-mediated CMA 111, 42.7%). The rate of children acquiring oral tolerance after 12 months was significantly higher (P < .05) in the groups receiving EHCF (43.6%) or EHCF + LGG (78.9%) compared with the other groups: RHF (32.6%), soy formula (23.6%), and amino acid based formula (18.2%). Binary regression analysis coefficient (B) revealed that the rate of patients acquiring tolerance at the end of the study was influenced by 2 factors: (1) IgE-mediated mechanism (B -2.05, OR 0.12, 95% CI 0.06-0.26; P < .001); and (2) formula choice, such that those receiving either EHCF (B 1.48, OR 4.41, 95% CI 1.44-13.48; P = .009) or EHCF + LGG (B 3.35, OR 28.62, 95% CI 8.72-93.93; P < .001). CONCLUSIONS: EHCF accelerates tolerance acquisition in children with CMA if compared with other dietetic choices. This effect is augmented by LGG.

The Potential Therapeutic Efficacy of Lactobacillus GG in Children with Food Allergies.

Food allergy (FA) continues to be a growing health concern for infants living in Western countries. The long-term prognosis for the majority of affected infants is good, with 80-90% naturally acquiring tolerance by the age of five years. However, recent studies suggest that the natural history of FA is changing, with an increasing persistence until later ages. The pathogenesis of FA as well as oral tolerance is complex and not completely known, although numerous studies implicate gut-associated immunity and enteric microflora, and it has been suggested that an altered composition of intestinal microflora results in an unbalanced local and systemic immune response to food allergens. In addition, there are qualitative and quantitative differences in the composition of gut microbiota between patients affected by FA and healthy infants. These findings prompted the concept that specific beneficial bacteria from the human intestinal microflora, designated probiotics, could restore intestinal homeostasis and prevent or alleviate allergy, at least in part by interacting with the intestinal immune cells.

Serum and intestinal celiac disease-associated antibodies in children with celiac disease younger than 2 years of age.

OBJECTIVES: In children younger than 2 years of age, a diagnosis of celiac disease (CD) is difficult to make because anti-endomysium (anti-EMA)/anti-tissue transglutaminase 2 (anti-TG2) antibodies are less sensitive than in older children. The aim of our study was to evaluate how many children younger than 2 years of age and diagnosed with CD, were negative for serum anti-TG2 antibodies and to test the hypothesis that in these patients, TG2-specific IgA deposits could instead be present at mucosal level. PATIENTS AND METHODS: A total of 104 children younger than 2 years of age and 179 children older than 2 years, all of whom had been diagnosed with CD, were investigated for serum CD-associated antibodies (anti-gliadin [AGA] IgA and IgG, EMA-IgA, anti-TG2-IgA). The presence of intestinal anti-TG2 extracellular IgA deposits was searched by using double immunofluorescence in 56 of the patients younger than 2 years of age and in 40 of those who were older than 2 years. RESULTS: In children with CD who were younger than 2 years of age, high levels of AGA-IgA were found in 93/104 (89%) and 98/104 (94%) were found of have high levels of AGA-IgG. In children older than the age of 2 years with CD, 120/179 (67%) had high levels of AGA-IgA and 151/179 (84%) had high levels of AGA-IgG. Serum EMA were present in 92/104 (88%) in the younger group and in 176/179 (98%) of the older group. Ninety-one of 104 children (87%) younger and 172/179 (96%) older than 2 years showed high serum levels of anti-TG2. Finally, 41/56 (73%) children younger than 2 years and all of the 40 children (100%) older than 2 years of age showed mucosal anti-TG2-IgA deposits. CONCLUSIONS: EMA and anti-TG2-antibody measurements show higher sensitivity for the diagnosis of CD in children older than 2 years compared with younger children. The search for mucosal deposits of anti-TG2-IgA does not improve the diagnostic performance.

Italian paediatricians' approach to coeliac disease diagnosis.

The aim of this study was to investigate the current implementation of the 1990 ESPGHAN criteria for the diagnosis of celiac disease (CD) in Italy to form a foundation for their revision. From September 2006 to March 2007 a nationwide questionnaire concerning current diagnostic methods was sent by mail to 54 Italian centres for the diagnosis of CD, which were distributed across the entire national territory. The questionnaire investigated the tests performed, diagnostic criteria currently used, and the management of some special cases in each centre. Eighty percent of the centres use anti-tissue transglutaminase to diagnose CD and anti-endomysium antibodies to confirm the results. Fifty-five percent still use anti-gliadin antibodies. A total of 87.5% of centres perform HLA typing, especially in first-degree relatives and in unclear diagnosis. Regarding histology, 67.5% of centres consider an infiltrative lesion consistent with diagnosis of CD. The majority of centres (85%) use the 1990 ESPGHAN criteria for both symptomatic and asymptomatic patients, but 80% do not perform a second biopsy in asymptomatic cases or a gluten challenge in children younger than 2 years of age. Furthermore, most centres (72.5%) do not prescribe a gluten-free diet to asymptomatic patients with positive serology and normal bowel architecture (ie, potential cases), but they do program a careful follow-up. In conclusion, ESPGHAN criteria are widely followed by Italian CD centres. However, their revision may be useful, but it should be evidence based. Large, multicentre studies are greatly needed.

Issues related to gluten-free diet in coeliac disease.

PURPOSE OF REVIEW: In the last few years, knowledge about coeliac disease has significantly improved, resulting in a better understanding of disease pathogenesis, diagnosis and therapy. This review describes the latest progress in research concerning treatment with gluten-free diet in patients with coeliac disease. RECENT FINDINGS: Gluten-free diet is generally admitted as effective therapy in symptomatic patients, but a life-long dietary treatment in some challenging cases such as 'silent' and 'latent' patients is under discussion. Tolerance to gluten may be acquired later in life, but, as latency may be transient, a strict follow-up is necessary in these patients. The composition of gluten-free diet needs a better definition; latest evidence demonstrates that oats are tolerated by most patients with coeliac disease. Finally, the amount of gluten permitted in gluten-free products is still a matter of debate; significant progress has been made in the sensitivity of techniques for gluten detection, but the daily amount of gluten that can be safely consumed is not yet defined. SUMMARY: Gluten-free diet remains the cornerstone of therapy of coeliac disease. More studies addressing the need of gluten-free diet for cases of 'potential' coeliac disease are necessary, as well as studies linking the best available analytical detection of gluten to the clinical threshold of tolerance.